Gene therapy of adenovirus mediated CD ::upp/5-FC directed by GSTP1 promoter in cisplatin-resistant ovarian cancer

Gynecol Oncol. 2005 Mar;96(3):643-50. doi: 10.1016/j.ygyno.2004.09.066.

Abstract

Purpose: To evaluate the specific killing effect of the adenoviral vector in which CD ::upp genes were directed by the GSTP1 promoter on cisplatin-resistant ovarian cancer cells.

Experimental design: Cisplatin-sensitive (A2780) and cisplatin-resistant (AD6) ovarian cancer cells were infected with recombinant adenoviral plasmid carrying the CD ::upp gene driven by the GSTP1 promoter and followed with 5-FC administration.

Results: In vitro, when MOI was 100 and 5-FC was 250 microg/ml, relative survival rate of the AD6 cells was only 3.63 +/- 1.01%, while under the same conditions, A2780 cells were 76.50 +/- 2.81%. Significant bystander effect was caused by the CD ::upp gene and 20% of gene-transferred AD6 cells caused death to 80.3% of the total cells. Furthermore, a significant anti-tumor effect of the Ad.GST-CD ::upp/5-FC was observed in nude mice bearing tumors of AD6 cells.

Conclusions: These results indicated that adenovirus-mediated Ad.GST-CD ::upp/5-FC directed by GSTP1 promoter is an effective approach to overcome cisplatin-resistant ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Artificial Gene Fusion
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cytosine Deaminase / genetics
  • Cytosine Deaminase / metabolism
  • Drug Resistance, Neoplasm
  • Female
  • Flucytosine / pharmacokinetics
  • Flucytosine / therapeutic use
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Glutathione S-Transferase pi
  • Glutathione Transferase / genetics*
  • Humans
  • Isoenzymes / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy*
  • Pentosyltransferases / genetics*
  • Pentosyltransferases / metabolism
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Isoenzymes
  • Recombinant Fusion Proteins
  • Flucytosine
  • Pentosyltransferases
  • uracil phosphoribosyltransferase
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Gstp1 protein, mouse
  • Cytosine Deaminase
  • Cisplatin